‘PATH to PD’ Program Seeks to Deepen Understanding of Parkinson’s Onset, Progression

‘PATH to PD’ Program Seeks to Deepen Understanding of Parkinson’s Onset, Progression

The Michael J. Fox Foundation for Parkinson’s Research (MJFF) will fund a new program to investigate the pathogenesis of Parkinson’s disease called “PATH to PD.”

The two-year program includes three research teams that will collaborate to investigate risks associated with genetics, environment and aging, while working with a common framework to gain a better understanding of the onset and progression of Parkinson’s.

Each PATH to PD-funded project will receive $2 million.

“The vast diversity of pathways implicated in Parkinson’s pathology to date indicates that multiple physiological routes can lead to PD, and these routes may intersect or be temporally dependent,” Todd Sherer, PhD, CEO of MJFF, said in a press release. “Through PATH to PD, our Foundation aims to encourage researchers to bring a holistic new approach to bear on refining today’s understanding of what Parkinson’s is — so that we can better strategize how to slow or stop the disease.”

Parkinson’s is not fully understood by scientists. Even though it is known the disease stems from gene-environment interactions as we age, the emerging picture of Parkinson’s is that of a vast, interwoven network culminating in a disease that varies greatly in cause, rate of progression, symptomology and treatment response.

All three teams will collaborate to build a common framework linking mechanisms through which genetics, environment and aging-associated risk and causal factors may lead to Parkinson’s disease.

University of Pittsburgh researchers, led by J. Timothy Greenamyre, MD, PhD, will seek out links between environmental and genetic triggers of the disease. Researchers will look into the mechanisms that lead neurotoxins to cause neurodegeneration and how these pathways are involved in interactions with genetic factors such as LRRK2 (leucine-rich repeat kinase 2), the leading genetic cause of the disease.

National Institutes of Health researchers, led by Andrew Singleton, PhD, will map the genetic effects in Parkinson’s by growing nerve cells from induced pluripotent stem cells, and map how various genetic alterations lead to the molecular and cellular changes associated with Parkinson’s.

Northwestern University researchers, led by D. James Surmeier, PhD, will investigate the link between aging and Parkinson’s. Using advanced gene-editing techniques, they will look at how cellular aging and related DNA and mitochondrial damage contribute to neurodegeneration in rodent and human cells.

These efforts have the common goal of developing a disease-modifying treatment for Parkinson’s disease, so that it can stop or slow disease progression.

For disease-modifying treatments to work best, however, they should target key underlying disease-causing pathways, which need to be identified and isolated first.

Some cases of Parkinson’s occur due to genetic factors, known as familial Parkinson’s disease. However, familial Parkinson’s is only a small fraction of all diagnoses of the disease. Informed guesses lean toward  environmental factors, including heavy metal or pesticide exposure, since aging still accounts for the greatest risk factor underlying this disease.

The fact that there is no identifiable cause of immediate contamination, researchers suspect this might be due to a lifetime accumulation of otherwise minor compound exposures that eventually lead to the development of the disease or contribute to a “switch” in Parkinson’s risk genes. Perhaps the process occurs naturally as medicine allows us to live longer, or perhaps it’s a combination of both.

“With Parkinson’s prevalence expected to double by 2040 to nearly 13 million people worldwide, our Foundation believes it is our obligation to continue building on current research momentum to eradicate this disease once and for all,” Sherer added.

3 comments

  1. J. Spanley says:

    Thank you for the information you make available to me. I was diagnosed 12 years ago, am now 81 and am very aware of the disease in me. I am full-care to my 83 year old husband and with the care of my PD and motion specialist, Dr. Dashtipour, I am still able to care for my partner of 64 years. BUT I know it will not last. Please continue sharing your information. We have no where else to go. Mr. Fox is an example that I carry with me. When things get rough I remember him and all the years I did NOT have P.D

  2. Our work has previously shown a younger age at onset which was duration of exposure dependent among subjects with sporadic PD exposed to metals and pesticides. But our findings also showed that exposure to metals and pesticides only accounted for about 15% of the difference in age at onset indicting that other factors such as genetics are at play. In support of this, other investigators have found a younger onset among subjects exposed to herbicides who also carry a mutant form of glutathione-S-transferase, an enzyme that plays a role in detoxification of xenobiotics. All that said, if we could delay disease onset by this same 15% or about 10 years it would be huge advancement from a public health perspective. But since doing this will likely require lifestyle changes decades before disease onset, it may be prudent for people who are concerned about developing PD to avoid/reduce their exposures to neurotoxicants sooner than later rather than waiting for the all the data to come in.

  3. Antonio Gagliardo says:

    My name is Antonio Gagliardo, a retired Carabinieri’s General of 76 year-old. My PD lasts 7 to 8 years. So far I fitghted agaist it by taking medicins (sinemet 100+25 and jumex 10mg) associated with a strong will of dynamic life, especially practicing saill in many contents nd olther home-works, since the onsets of my PD. It wolked very well till 4-5 months ago. So that I need more medicins. My only Parkinson’s problem is on-off associated with slowness of movements, especially in afternoon. The therapy has been growed gradually for sinemet’s number, not the same for jumex (passing by 5mg to 10mg.
    My my work for a lon time (about 50 yers working in many places around the world) has given me to live in very different environment. No familiar PD.

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